Discussion:
Given the keratinophilic nature of dermatophytes, invasion deeper than
the stratum corneum in the skin is rare.1 However,
this case demonstrates that increased immunosuppression in patients with
superficial dermatophyte infections may predispose to angioinvasive
disease involving deeper tissues. The most common predisposing factors
associated with invasive dermatophyte infections include: superficial
dermatophytosis, solid organ transplant, topical immunosuppressants,
gene mutations, diabetes, and trauma.6 The development
of our patient’s angioinvasive dermatophyte infection was preceded by
increasing immunosuppression with high dose steroids, rituximab, and
ibrutinib in the setting of worsening CLL and ITP. It is known that
immunosuppressive agents used in hematologic malignancies such as bruton
tyrosine kinase inhibitors (ibrutinib) and anti-CD20 monoclonal
antibodies (rituximab) are associated with an increased risk of invasive
fungal infection.7-10 Classically, these fungal
infections include invasive yeast infections such as candidiasis, mold
infections including aspergillosis and fusariosis, endemic fungal
disease, and classic opportunistic infections such as cryptococcus and
pneumocystis jiroveci.8 Invasive dermatophyte
infections are rarely considered when increasing a patient’s
immunosuppression. In the setting of superficial dermatophyte
infections, clinicians should be aware of the possibility of invasive
disease when increasing immunosuppression similar to the more classic
non-dermatophyte invasive fungal infections. When a superficial
dermatophyte infection presents with a dusky appearance and/or leads to
pain out of proportion to exam, there should be concern for invasive
disease, including necrotizing fasciitis, and early biopsy/surgical
intervention should be considered.
Antifungal treatment guidance for invasive dermatophyte infections is
scarce. When dermatophyte infections extend beyond the stratum corneum,
it is generally recommended to transition from topical to oral therapy.
There is not a consensus on the preferred oral antifungal. A recent
systematic review of invasive dermatophyte infections showed that the
most commonly used agents were terbinafine and
itraconazole.6 However, a number of patients were
treated with other antifungals including griseofulvin, fluconazole,
amphotericin B, and posaconazole.6 There was
additional variability in the duration of treatment for the cases
reviewed. We treated our patient with oral terbinafine 250 mg daily for
12 weeks. This drug, dose, and duration of therapy in combination with
surgical debridement and reduced immunosuppression resulted in clinical
clearance of infection.